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1、百草枯中毒（Parquat Poisoning),主讲人：张海英 副教授 10.11.04,Introduction,速效除草剂，接触土壤迅速失活联吡啶类除草剂，又名对草快经胃肠道、皮肤和呼吸道吸收,Mechanisms,不明。在细胞内形成过量自由基和过氧化物，引起细胞膜脂质过氧化，造成以肺为主的多器官损害。,Clinical Presentation,Local Lesion skin eye respiratory tracts mucous membrane,Clinical Presentation,Impairment of multiple organs：除大剂量中毒外多在1-7天
2、内多器官系统渐进式病变，lung injury常见而突出 Digestive system：早期恶心、呕吐、腹痛、腹泻及血便，2-3天中毒性肝病 Urinary system：急性肾功衰竭，多见于2-3天,Clinical Presentation,Respiratory system：最突出和最严重 大量口服者24-48h出现肺水肿或出血，常死于ARDS；小剂量中毒者早期可无呼吸道症状，少数有咳嗽、咳痰、呼吸困难、双肺干湿啰音、纵膈及皮下气肿，部分存活者1-2周后可发生肺间质纤维化，最终死于呼吸衰竭。,Clinical Presentation,Circulation system：中毒性心
3、肌损害，低血压、心电图改变 Nervous system：头晕、头痛、昏迷、抽搐 Hematological system：贫血和血小板减少,Degree Classification,Mild：摄入量20mg/kg，无症状或仅有粘膜改变，可出现呕吐、腹泻。Moderate to severe：摄入量20mg/kg，部分可存活，多数2-3周内死于肺功能衰竭。Explosion：摄入量40mg/kg.1-4日内死于多器官衰竭。,Diagnosis,Exposure+Clinical presentation+Laboratory findings血清样本必须是摄入百草枯4h后的，保在塑料试管内，
4、不能用玻璃管。,Management,早期处理：催吐并口服白陶土或泥浆水100-200ml。阻止毒物继续吸收：尽快脱去染毒衣物，用肥皂水彻底清洗，眼部污染用流水冲洗15min。洗胃及导泻。加速毒物排泄：最好在服毒后6-12h内血液灌流。,Management,防止肺纤维化：早期大量肾上腺皮质激素。中重度患者用环磷酰胺。自由基清除剂包括VitC、VitE、谷胱甘肽等。仅在氧分压40mmHg或ARDS时才用21%浓度的氧气或应用PEEP。对症与支持：保护消化道粘膜，保护肝、肾、心功能，维持水电酸碱平衡，积极控制感染。,有机磷农药中毒（Organophosphorous Pesticide Pois
5、oning),主讲人：张海英 副教授 10.11.04,有机磷农药（organophosphorous pesticide,）oiliness or crystal，alliaceousinhibition of cholinesterase and resultant accumulation of acetylcholine causes initial stimulation,then exhaustion of cholinergic synapesmanifest 3 different phases of toxic effects,namely,acute cholinergic
6、 crisis,intermediate syndrome and delayed polyneuropathy,Introduction,Category and toxicity,Hypertoxic:LD50 10mg/kg thimet(3911),demeton(1059),parathion(1605),omethoate,etc Relatively hypertoxic:LD50 10100mg/k methyl parathion,DDVP,etcModerately toxic:LD50 1001000mg/kg dipterex,dimethoate,etcHypotox
7、ic:LD50 10005000mg/kg malathion，chlorothion，etc,Etiology,1.Manufacture or transport2.Use the organophosphate3.Contamination4.Suicide,Absorption and Metabolism,Absorption gastrointestinal,respiratory tracts,skin and mucous membrane.The highest concentration in liver.Metabolization:mainly in the liver
8、.Some organophosphate compounds became more toxic oxydized by liver.Excretion:612hr reach peak blood concentration after absorption and excreted by kidney in 24hr,after 48hr completely excreted from body.,Mechanisms,对人畜的毒性主要在于抑制cholinesterase（CHE)。体内胆碱酯酶分为：真性：CNS、RBC、交感N节、运动终板 假性：白质、血清、肝、肠粘膜下层、腺 体中，
9、能水解丁酰胆碱，对乙酰胆 碱几无作用。,Mechanisms,constant acetylcholine receptor triggering,Inhibition of cholinesterase activity,acetylcholine accumulation at cholinergic synapses,cholinergic effects in peripheral and central nervous systems,Clinical Presentation,（一）Acute Cholinergic Crisis The onset of clinical pre
10、sentation will vary with the route,degree of exposure and physicochemical properties of the organophosphate.Time interval between exposure and symptoms is 26hr by skin,10min2hr by oral.,（一）Acute Cholinergic Crisis,1Muscarinic symptoms：主要是副交感神经末梢兴奋所致，出现最早，表现为：平滑肌收缩：瞳孔缩小，胸闷、气短、呼吸困难，恶心呕吐、腹痛、腹泻 括约肌松弛：大小
11、便失禁腺体分泌增加：大汗、流泪、流涎、气道分泌物增加（咳嗽、气促、双肺啰音、肺水肿）,（一）Acute Cholinergic Crisis,2 Nicotinic symptoms：交感N节受乙酰胆碱刺激，其节后交感N纤维释放儿茶酚胺：皮肤苍白、心率增快、心律失常、血压升高。横纹肌神经肌肉接头处ACh蓄积：肌颤、肌肉强直性痉挛，后期肌力减退或瘫痪，严重时呼吸肌麻痹导致呼吸衰竭或停止。,（一）Acute Cholinergic Crisis,3 CNS symptoms 头晕、头痛、疲乏、共济失调、烦躁不安、谵妄、抽搐、昏迷，严重者呼吸循环衰竭而死亡。,(二)bounce-back,急性有机磷
12、农药中毒，特别是乐果和马拉硫磷口服中毒者，经积极抢救临床症状好转，达稳定期数天至一周后病情突然急剧恶化，再次出现胆碱能危象，甚至发生昏迷、肺水肿或突然死亡。可能与皮肤、毛发和胃肠道内残留的有机磷农药被重新吸收及解毒药减量过快或停用过早等有关。,（三）中间型综合征 Intermediate syndrome(IMS),Occur within 24 96 hours or 2 7 days,between acute cholinergic crisis and delayed polyneuropathyRecovery needs 2-20d,even 1 monthmainly seen
13、in serious patients exposed to certain organophosphate,such as senthion、dimethoate、omethoate,（三）中间型综合征,characterised by muscle weakness:cranial nerve palsies,weakness of the neck and proximal limbs,and respiratory paralysisprolonged and severe acetylcholinesterase inhibition and a combined pre-and p
14、ostsynaptic impairment of neuromuscular transmission are proposed mechanisms,（四）Delayed Polyneuropathy,occurs 12 weeks after acute exposure to certain organophosphate insecticides.The clinical features are predominantly motor neuropathy and primarily manifest as numbness and weakness of the lower ex
15、tremities followed by progressive ascending weakness of limb muscles.mechanisms include inhibition of the neuropathy target esterase.,（五）Local Lesion,skin irritationeye irritation,Laboratory Findings,（一）血胆碱酯酶活力测定 Mild poisoning:5070%of normal Moderate poisoning:3050%of normal Severe poisoning:below
16、30%of normal（二）尿中OPI代谢物测定 对硫磷和甲基对硫磷 对硝基酚 敌百虫 三氯乙醇,Diagnosis,根据接触史、呼出气大蒜味、瞳孔缩小、多汗、肌纤维震颤、意识障碍等，可作出诊断。如全血CHE活力降低可确诊。不明原因意识障碍、瞳孔缩小、并伴有肺水肿者，要疑诊OPI中毒，测血ChE活力,Differential diagnosis,与其他农药鉴别：氨基甲酸酯类、拟除虫菊酯类、杀虫脒类农药；与相关症状的疾病鉴别：昏迷、瞳孔小：与鸦片及毒蕈和吩噻嗪中毒、桥脑出血鉴别；腹痛腹泻：与急腹症、食物中毒、中暑、胃肠炎鉴别 多汗：与低血糖、甲亢危象鉴别,Degree Classificati
17、on,Mild Poisoning：以M样症状为主。头晕头痛、恶心呕吐、出汗无力、视力模糊、胸闷等，瞳孔可能缩小。CHE活力70%-50%。Moderate Poisoning：M样症状加重，出现N样症状。尚有肌颤、瞳孔缩小、轻度呼吸困难、大汗流涎、腹痛腹泻、步态蹒跚、神志可模糊、血压可升高。CHE活力50%-30%。Severe Poisoning：除M、N样症状外，合并脑水肿、肺水肿、呼吸衰竭、抽搐、昏迷等。CHE活力30%以下。,Management,一、Decontamination立即脱离现场，脱去污染衣服，彻底清洗染毒皮肤、毛发和指甲洗胃（胃管反复洗胃）敌百虫忌用2%碳酸氢钠溶液洗
18、胃 对硫磷忌用1/5000高锰酸钾溶液洗胃硫酸镁20-40g口服导泻，眼部污染用2%碳酸氢钠或生理盐水冲洗hemoperfusion or hemodialysis：中毒后14天内行血液灌流或血液透析，每天一次，每次23小时,二、Use of specific antidotes（一）应用原则：早期、足量、联合、重复（二）cholinesterase reactivator：Reverses the cholinergic nicotinic effects and recovers cholinesterase activityrepresentative medicine：PAM-Cl、P
19、AM-Itarget：blood cholinesterase elevated rapidly to more than 50%of normal value,（二）cholinesterase reactivator,氯解磷定、碘解磷定对甲拌磷、内吸磷、对硫磷、甲胺磷疗效较好，对敌百虫、敌敌畏疗效稍差，对乐果、马拉硫磷基本无效。双复磷对敌百虫、敌敌畏疗效明显好于碘解磷定。对ChE复活剂疗效不佳者，以抗胆碱药治疗为主或两药合用。不良反应有眩晕、恶心、呕吐、视物模糊、血压升高、全身麻木和灼热感等。用量过大：癫痫样发作、呼吸抑制和抑制CHE力。,（三）anticholine drugs 作用机理
20、：与乙酰胆碱争夺胆碱能受体，阻断乙酰胆碱的作用。阿托品对解除M样症状和对抗呼吸中枢抑制有效。atropinization：瞳孔较前扩大、口干、皮肤干燥、颜面潮红、HR加快、肺部罗音消失等，应逐步减少阿托品用量阿托品中毒：瞳孔明显扩大，出现神智模糊、烦躁不安、谵妄、惊厥、昏迷及尿潴留等，应立即停用，酌情毛果芸香碱对抗，必要时血液净化。阿托品与胆碱酯酶复活剂联合应用,（三）anticholine drugs,盐酸戊乙奎醚（长托宁）：对外周M受体和中枢M、N受体均有作用，长托宁化：与阿托品化相似，但心率增快不作为判断标准。长托宁较阿托品具有优势：拮抗M样症状效应更强有较强拮抗N受体作用有中枢和外周双
21、重抗胆碱效应，且中枢作用强于外周不引起心动过速半衰期长，无需频繁给药每次所用剂量小，中毒发生率低。故目前推荐为急救首选抗胆碱药物。,（四）Supportive Care 重在维护心、肺、脑等生命器官功能：保持呼吸道通畅，正确氧疗，必要时机械通气肺水肿时以阿托品治疗为主休克者给予血管活性药物脑水肿者予甘露醇和糖皮质激素脱水按心律失常类型选用适当抗心律失常药物危重者可血液净化治疗重度中毒留院观察至少37天以防复发,（五）Management of IMS 以人工机械通气为主，给以足量氯解磷定，重复应用23天。,（六）Management of DPN 肌注大量VB1、B12,应用胞二磷胆碱及肾上腺皮质激素，辅以物理治疗及支持疗法。,THANK YOU,
